Most of conventional chemotherapeutic agents for cancer exert an anticancer effect by directly inhibiting DNA biosynthesis of cells and act effectively against tumors that are active in cell division.
However, since normal cells as well as cancer cells are in vivo active in cell division, the existing chemotherapeutic agents for cancer are insufficient in selective toxicity to cancer cells, causing strong side effects. Therefore, there has been a problem in that chemotherapeutic agents for cancer are not able to be administered in an amount enough to exert their anticancer effect.
Further, in contrast to the chemotherapy that directly kills cancer cells, there have been attempted a differentiation-inducing therapy that induces differentiation of cancer cells to put them back to normal cells, hyperthermia which takes advantage of vulnerability of cancer cells to heat, a vasopressor chemotherapy which makes use of undeveloped blood circulatory system of cancer cells and their peculiarity, a method utilizing drug delivery system (DDS), as well as a missile treatment using a monoclonal antibody which attacks cancer cells only or the same antibody condensed with an anticancer agent.
In recent years, analysis of characteristics of cancer cells and a canceration mechanism has rapidly progressed at a molecular and genetic level. Accordingly, unprecedented approaches to the cancer therapy aimed at a new target have been attempted, for example, a method using a drug resistance overcoming agent, a cancer metastasis inhibitor or a vascularization inhibitor, as well as a gene therapy using a gene-carrying vector.
However, there has not been found a satisfactory anticancer agent or therapy that surely inhibits cancer proliferation and hardly causes side effects. Therefore, development of them has been longed for.
In general, cancer cells repeat rapid proliferation. Therefore, uptake of essential amino acids which cannot be produced by intracellular metabolism is abnormally accentuated.
The inventors of the present invention have succeeded in molecular cloning of a cancer-specific L-type amino acid transporter, which is a membrane protein required for intracellular uptake of neutral branched-chain amino acids and aromatic amino acids containing many essential amino acids, and named it as L-type amino acid transporter 1 (LAT1) (Kanai Y. et al., Journal of Biological Chemistry, 273, 23629(1998)). It has also been confirmed that an L-type amino acid transporter (LAT2), which is a membrane protein indispensable for uptake of the essential amino acids, exists even in normal cells (Japanese Unexamined Patent Publication No. 2000-342270 etc.).
Accordingly, it is considered that screening of substances which strongly act against LAT1 allows specifically inhibiting the expression of LAT1, which may possibly constitute the rate-determining step of the cancer cell proliferation.
As the only compound which specifically inhibits the amino acid transport system L (LAT), 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is known. However, its inhibiting action is very weak and there has not been reported that it has an inhibiting action against the cancer cell proliferation.